Is OSBPL2 p.Ser20Pro (c.58T>C) pathogenic?

OSBPL2 p.Ser20Pro (c.58T>C) is classified Uncertain significance in OSBPL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.0761); Ultra-rare (popmax 0.0307%, afr); Associated with Inborn genetic diseases.

What condition is associated with OSBPL2 p.Ser20Pro (c.58T>C)?

OSBPL2 p.Ser20Pro (c.58T>C) is associated with Inborn genetic diseases (ClinVar).

How common is OSBPL2 p.Ser20Pro (c.58T>C) in the general population?

OSBPL2 p.Ser20Pro (c.58T>C) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about OSBPL2 p.Ser20Pro (c.58T>C)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

OSBPL2 p.Ser20Pro

c.58T>C · rs368593317 · VCV2442703

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 0.64	GERP -3.6, phastCons 0.92
Regional constraint	o/e 1.07	unconstrained · MANE · 7,438 bp · p 0.55 · regional, not allelic
Overall
CADD	15.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,886 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00149% 24/1,613,886 alleles · ultra-rare exomes 12/1,461,768 · genomes 12/152,118 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,256
Admixed American	0.00167%	59,994

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: OSBPL2
Protein: p.Ser20Pro
Coding: c.58T>C
MANE Select: NM_144498
dbSNP: rs368593317
Type: single nucleotide variant
Location: chr20:62260001 (GRCh38)
Gene constraint: LOEUF 0.467 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 83.92 · 1 PDB
Residue 20: the 'disordered' region; a modified residue (phosphoserine)

Full OSBPL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OSBPL2 p.Ser20Phe Uncertain significance ★ ⚠ same residue
OSBPL2 p.Arg434Trp Uncertain significance ★★ same condition
OSBPL2 p.Asp475Asn Uncertain significance ★★ ⚠ same condition
OSBPL2 p.Gln58Pro Uncertain significance ★★ ⚠ same condition
OSBPL2 p.Glu284Gly Uncertain significance ★★ same condition
OSBPL2 p.Gly245Arg Uncertain significance ★★ ⚠ same condition
OSBPL2 p.Ile34Val Uncertain significance ★★ ⚠ same condition
OSBPL2 p.Ile479Thr Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/osbpl2-p-ser20pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown